We wish to continue our investigations into the etiologic role of activated complement/neutrophil interaction in shock lung. In our previous studies of the nature of hemodialysis neutropenia, we demonstrated that extracorporeal complement-activation (by dialysis coil cellophane) leads to increased granulocyte adhesiveness and aggregation. This results in sequestration of granulocytes in the pulmonary microvasculature when the activated plasma is reinfused; in addition, pulmonary endothelial damage with extravascular leak of high-protein edema fluid also occurs. Since pulmonary leukostasis and high-protein pulmonary edema are cardinal features of shock lung, we wish to discern whether the syndrome - although accompanying diverse clinical insults such as shock, sepsis, acute pancreatitis, and extracorporeal circulation - results from a single common phenomenon, to wit: prolonged complement activation. We propose to study the effects of purposeful complement activation on pulmonary ultrastructure, function, vascular response, and granulocyte function/kinetics. These in vivo studies will be performed simultaneously with in vitro studies of modulators of complement-induced granulocyte aggregation and cultured endothelial-cell cytotoxicity. The effects of pharmacologic agents used in the treatment of shock lung, such as corticosteroids, will particularly be examined. Finally, sequential assays for C5a using granulocyte aggregometry will be performed on plasma from patients at risk for developing shock lung in an attempt to document a temporal (?causal) role for this C fragment.